The Joint Annual Scientific Meetings of the Endocrine Society of Australia and the Society for Reproductive Biology 2018

Role of Hepatocyte Vitamin D Signalling in Liver Fibrosis (#185)

Jeremy T Keane 1 2 , Christopher Liddle 2 , Jenny E Gunton 1 2
  1. Centre for Diabetes, Obesity and Endocrinology, Westmead Institute for Medical Research, Westmead, NSW, Australia
  2. Faculty of Medicine and Health, Sydney University, Westmead Hospital, Westmead, NSW, Australia

Objective: To investigate whether Vitamin D signalling in hepatocytes ameliorates liver fibrosis.

Methods & Results:  Hepatocyte vitamin D receptor (h-VDR) knockout (KO) mice and their floxed controls (FC) were created. Mice were subjected to twice weekly intraperitoneal injections of thioacetamide (TAA) or saline for 10 weeks and subsequently sacrificed. The liver sections of mice from the h-VDR KO group demonstrated increased fibrosis staining and collagen compared to those of the FC group. qPCR results show an increase in mRNA levels of TNFa, and TIMP1, markers of hepatic inflammation, in the KO group when compared to the FC group, as well as increased mRNA levels of the macrophage marker F480, indicating that liver macrophage infiltration was increased by loss of h-VDR.

Conclusions: h-VDR may play a role in modulating chronic liver injury. These hepato-protective effects may be of therapeutic use in human liver disease.

Lay description: Liver Vitamin D Receptor (VDR) may play a role in modulating chronic liver injury, as indicated by our TAA model. Mice lacking hepatocyte VDR, the receptor through which Vitamin D functions, had increased markers for liver fibrosis compared to those with a functioning VDR.